Cardiovascular diseases remain America's primary killer by a large margin, claiming the lives of more Americans than the next two main causes of death combined (cancer and pulmonary complications). In particular, coronary artery disease (CAD) is by far the most lethal, causing 17% of all (cardiac-related or not) deaths every year. One of the main reasons for this high death toll is the severe lack of effective and accessible imaging tools upon anomaly detected on the electrocardiogram (ECG), especially at the early stages when CAD can be stabilized with appropriate pharmacological regimen. The long-term goal of our studies is to establish the potential of a low-cost, portable, noninvasive and reliable strain imaging technique of Myocardial Elastography pioneered by our group for early detection and localization of myocardial ischemia. In this renewal study, we propose to overcome all limitations identified during the past funding period and ensure clinical translation for detection of ischemia and differentiation from infarction. Our group was the first to demonstrate that cardiac strain imaging using parallel beamforming is feasible 1) at extremely high frame rates (up to 2000 fps) ensuring 2) high precision and 3) angle-independent 2D strain estimates, 3) 3D capability, 4) imaging of transient cardiac events (~1-10 ms electromechanical strains) and 5) real-time implementation 6) without ECG gating or breath holds. Therefore, the hypothesis of this study is that parallel- beamforming Myocardial Elastography (PBME) will have increased sensitivity for 1) detection of early onset of ischemia that current modalities may miss and 2) differentiation of early onset from advanced ischemia or infarction based on the resulting altered mechanical and electromechanical cardiac function. The specific aims are as follows: 1) characterize fundamental performance of PBME in simulations and phantoms; 2) validate PBME detection of early disease onset in canines in vivo; and 3) validate PBME findings against CT angiography and nuclear perfusion. High reliability of PBME for detection and characterization of early ischemic onset would entail its readily translation and seamless integration in the clinical echocardiography routine.